Inhibitory effects of aripiprazole on interferon-γ-induced microglial activation via intracellular Ca2+ regulation in vitro

Takahiro Kato, Yoshito Mizoguchi, Akira Monji, Hideki Horikawa, Satoshi O. Suzuki, Yoshihiro Seki, Toru Iwaki, Sadayuki Hashioka, Shigenobu Kanba

Research output: Contribution to journalArticle

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Abstract

The activation of the inflammatory/immunological response system is suggested to be related to the pathophysiology of schizophrenia. Aripiprazole is a novel atypical antipsychotic, which is a high-affinity dopamine D2 receptor partial agonist. Atypical antipsychotics, all of which have dopamine D2 receptor antagonism, have recently reported to have significantly inhibitory effects on interferon (IFN)-γ-induced microglial activation in vitro. In the present study, we investigated whether or not aripiprazole also has anti-inflammatory effect on IFN-γ-induced microglial activation. Not quinpirole, dopamine D2 full agonist, but aripiprazole significantly inhibited the generation of nitric oxide (NO) and tumor necrosis factor (TNF)-α from IFN-γ-activated microglia and suppressed the IFN-γ-induced elevation of intracellular Ca2+ concentrations ([Ca2+]i) in murine microglial cells. Increased [Ca2+]i has been reported to be required, but by itself not sufficient, for the release of NO and certain cytokines. As a result, we can speculate that aripiprazole may inhibit IFN-γ-induced microglial activation through the suppression of IFN-γ-induced elevation of [Ca2+]i in microglia. Our results demonstrated that not only antipsychotics which have dopamine D2 receptor antagonism but also aripiprazole have anti-inflammatory effects via the inhibition of microglial activation. Antipsychotics may therefore have a potentially useful therapeutic effect on patients with schizophrenia by reducing the microglial inflammatory reactions.

Original languageEnglish
Pages (from-to)815-825
Number of pages11
JournalJournal of Neurochemistry
Volume106
Issue number2
DOIs
Publication statusPublished - Jul 1 2008

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Interferons
Chemical activation
Antipsychotic Agents
Dopamine D2 Receptors
Microglia
Schizophrenia
Nitric Oxide
Anti-Inflammatory Agents
Quinpirole
Therapeutic Uses
Aripiprazole
In Vitro Techniques
Dopamine
Tumor Necrosis Factor-alpha
Cytokines

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Cellular and Molecular Neuroscience

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Inhibitory effects of aripiprazole on interferon-γ-induced microglial activation via intracellular Ca2+ regulation in vitro. / Kato, Takahiro; Mizoguchi, Yoshito; Monji, Akira; Horikawa, Hideki; Suzuki, Satoshi O.; Seki, Yoshihiro; Iwaki, Toru; Hashioka, Sadayuki; Kanba, Shigenobu.

In: Journal of Neurochemistry, Vol. 106, No. 2, 01.07.2008, p. 815-825.

Research output: Contribution to journalArticle

Kato, Takahiro ; Mizoguchi, Yoshito ; Monji, Akira ; Horikawa, Hideki ; Suzuki, Satoshi O. ; Seki, Yoshihiro ; Iwaki, Toru ; Hashioka, Sadayuki ; Kanba, Shigenobu. / Inhibitory effects of aripiprazole on interferon-γ-induced microglial activation via intracellular Ca2+ regulation in vitro. In: Journal of Neurochemistry. 2008 ; Vol. 106, No. 2. pp. 815-825.
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